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Page 2 of 15 Bhangui et al. Hepatoma Res 2020;6:71 I http://dx.doi.org/10.20517/2394-5079.2020.67

4.276), AFP > 200 ng/mL at the time of recurrence (P =0.02, HR = 2.075, 95%CI: 1.121-3.841), and recurrence
at multiple sites (P = 0.047, HR = 1.831, 95%CI: 1.009-3.321) were poor prognostics factors for post recurrence
survival. Multimodality management of recurrence using combined medical, surgical, ablative treatments and
radiotherapy significantly improved survival compared to the use of TKI’s or mTORi’s alone, or in combination.

Conclusion: In patients accepted for LDLT beyond the conventional size-number criteria, even after HCC recurrence,
an aggressive approach using multimodality therapy, when possible, aids in further prolongation of survival.

Keywords: Living donor liver transplantation, hepatocellular carcinoma recurrence, multimodality treatment,
outcomes, prognostic factors

INTRODUCTION
Liver transplantation (LT) is now accepted as the best curative option for hepatocellular carcinoma
(HCC) in patients with decompensated liver disease as it achieves oncological clearance, and also treats
[1]
the underlying chronic liver disease (CLD) . This however holds true when selection of patients for
[4-9]
[3]
[2]
LT adheres to either the conventional Milan and UCSF criteria, or other expanded criteria which
have also yielded similar long term outcomes. Over the years, the focus of selection has shifted from size
and number of tumours on pre-LT imaging, to tumour biology. Inclusion of tumour markers like alpha
fetoprotein (AFP) and des-gamma-carboxy- prothrombin (DGCP), grade of the tumour, and FDG-18 PET
scan avidity in the selection criteria, indicates the increased recognition that tumour biology is crucial
and dictates long term outcome [10-13] . The main determinant of long term outcomes in HCC patients after
LT is indeed tumour recurrence, and it continues to be the Achilles heel of this curative strategy. With an
expansion of criteria, the chance of recurrence tend to be higher. It is still believed that recurrence leads to
early death in most cases, since management of post-LT HCC recurrence to prolong survival remains very
challenging. Recurrences frequently occur within the first 2 years after LT, however very late recurrence
after a 10 year period have also been reported [14-16] . Furthermore, recurrences tend to occur as extrahepatic
disease (as high as 71%), followed by intrahepatic recurrence alone, and both intra- plus extrahepatic
recurrence . Given that recurrence more often occurs at multiple sites, treatment of recurrence is even
[17]
more difficult, and mostly limited to systemic therapy alone. Tumour burden at the time of recurrence is
also a major determinant of outcomes (single vs. multiple nodules at the time of recurrence). The options
available for systemic therapy are few, including tyrosine kinase inhibitors, and the recently introduced
checkpoint inhibitors. Results using these systemic agents are far from satisfactory, and they are known to
prolong survival only by a few months.

In this study, we analyzed our results in managing patients with HCC recurrence post-LDLT with the use
of multimodality treatment including surgical resection, ablative treatment, radiotherapy, modulation of
immunosuppression, and systemic agents.

METHODS
Selection criteria for LT in patients with cirrhosis and HCC
At our center, we accept medically fit HCC patients for living donor liver transplantation (LDLT)
irrespective of tumor size and number, provided they have no extrahepatic disease, or major vascular
invasion. Listing for deceased donor liver transplantation is based on the UCSF criteria. Pre-LT recipient
evaluation in HCC patients includes a whole body FDG-18 PET scan with triphasic CT angiography
abdomen (or dynamic contrast MRI in recipients with borderline renal function), and whole body Tc-99m
bone scan to rule out extent of hepatic, as well as extrahepatic spread. Alpha-fetoprotein (AFP) levels are
also measured.